10BloodMajor ThemesThe cellular elements of blood have a short life span and require continuous replacement. White blood cells play a critical role in defending the body against microbes and other foreign substances. Red blood cells transport oxygen from the lungs to tissues and return carbon dioxide. Platelets are cell fragments critical in the prevention and control of hemorrhage. Certain plasma proteins are important in body defenses, in the transport of essential substances, in maintaining blood volume, and in blood clotting. Numerous nutrient and waste substances are dissolved in plasma.

Chapter ObjectivesOverview of Blood 3761. List five functions of blood, and list theblood component related to each function. Be as specific as possible.

4. Compare and contrast acute inflammation,chronic inflammation, parasitic inflammation, and allergies, and list the cells involved in each.

Erythrocytes and Oxygen Transportblood cells and explain the functional implications of each characteristic.

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5. List three physical characteristics of red

2. Name the three types of plasma proteinsand roles of each.

Leukocytes, Inflammation, and Immunity 3833. Classify leukocytes based on theirappearance and function.

6. Describe the structure and function ofhemoglobin.

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7. Describe the life cycle of a red blood cell. 8. Discuss the diagnosis and possible causes ofanemia.

12. Use flowcharts to illustrate the tissue factorpathway, contact activation pathway, and common pathway of blood clotting, and explain how two different anticoagulants work.

9. Discuss the pathway that results in increased redcell production in individuals living at high altitudes.

13. List three differences between coagulation andthrombosis.

Platelets

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Blood Groups and Transfusion

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10. Describe the regulation and mechanism ofplatelet synthesis and the problems associated with thrombocytopenia.

14. Determine which blood group can be transfusedinto patients with A, B, O, or AB blood, and explain why agglutination reactions occur.

Hemostasis

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Bone Marrow Failure: The Case of Eleanor B. 40315. Use the case study to explain the central role ofbone marrow in blood cell production and to discuss the roles of erythrocytes, platelets, and leukocytes.

11. Use diagrams to explain the three steps ofhemostasis.

My life is running out of my nose!As you read through the following case study, assemble a list of the terms and concepts you must learn in order to understand Eleanors case. Clinical History: Eleanor B., a 52-year-old professor of anthropology, presented to the emergency room of a large metropolitan hospital with a severe nosebleed. I never have nosebleeds. This takes the cake; it just wont stop. My life is running out of my nose! Questioning by hospital staff revealed that 8 years earlier she had surgery for breast cancer. Physicians had followed her closely until 3 years earlier, when she divorced and moved to her current job in a new city. Im embarrassed to admit that I havent seen a doctor in three years, she said. Ive just been too busy to have my regular checkups. Further questioning revealed nothing medically unusual. She mentioned, however, having felt unusually tired in the last few months. I seem to wear out at even the smallest tasks. Last week I stopped for a rest on a park bench on my way home. Thats never been necessary before. Physical examination and other data: Eleanor was pale, and her skin contained numerous pinpoint hemorrhages. Otherwise her physical examination was unremarkable. Blood analysis revealed a marked deficiency in red blood cells, white blood cells, and platelets. Her blood type was determined to be O positive. Clinical course: In the emergency room her nose was packed with cotton strips and she was transfused with platelets, which stopped the nosebleed. She was admitted to the hospital and transfused with red blood cells. Knowing that breast cancer has a tendency to spread to bones, the examining physician suspected that cancer cells had taken over her red bone marrow, the site of blood cell production. This theory was confirmed by a bone marrow biopsy, which showed nearly complete replacement of normal bone marrow by cancer cells.

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Need to KnowIt is important to understand the terms and concepts listed below before tackling the new information in this chapter. Osmosis, cell structure, stem cells, properties of connective (Chapter 3) tissues Chemical signaling, hormone regulation (Chapter 4)

She was treated with additional chemotherapy but continued to need red blood cell transfusions to maintain hemoglobin near the normal level, and she required antibiotic treatment on several occasions for bacterial infectionspneumonia, skin abscesses, and recurrent diarrhea. Nine months later she was brought to the emergency room by ambulance for severe bloody vomiting. She was pale and confused, with blood pressure 60/20 mm Hg (normal: 120/80) and heart rate 140 beats per minute (normal: 70). Despite heroic efforts to save her, her heart stopped and could not be restarted. Lab studies from blood collected before her death showed the counts of red and white blood cells and platelets to be very low. Staphylococcus aureus, a bacterium, was cultured from her blood. At autopsy, the bone cavities normally containing red marrow were filled with tumor; little normal marrow remained. She was also found to have severe bacterial pneumonia and an extensive fungal infection in her esophagus. The latter had produced a large esophageal ulcer, which was the source of her fatal hemorrhage.

Our earliest ancestors recognized that blood was vital to life: whether gushing from man or mastodon, it was a warm, red, sticky fluid that carried away with it the victims life force. Honoring its importance, ancient peoples used blood in sacrificial rites, and the color of blood has come to symbolize valor and vitality. Eastern European folklore describes vampirescreatures who, by drinking fresh blood, could stave off death. Its not such a far-fetched ideaeven today we take blood from one person to give to another for that very purpose. So what, exactly, is this life-sustaining fluid that we hold so dear?

Dont worry; the bleeding always stops.Advice from older surgeons to worried younger ones.

Overview of BloodBlood is the fluid circulated by the heart through the blood vessels. Blood cells are made by the bone marrow and released into blood. Recall from Chapter 3 that we defined blood as liquid connective tissue. It fits that classification for two reasons: (1) functionally, it connects various parts of the body by carrying chemical signals, fluids, and nutrients from one place to another; (2) structurally, it contains cells and a large amount of extracellular matrix (plasma),

which in the case of blood, is liquid rather than solid. In addition, like cells in solid connective tissues, blood cells require nutrients, produce wastes, die, and are replaced by new cells. But although classified as connective tissue, blood has certain distinctive properties that set it apart from other tissues: Blood cells are in continuous motion. The life span of blood cells is unusually short, varying

from a few hours to a few months. Blood is redbright red if well oxygenated (on the

way to tissues from the lungs), dark reddish-blue if

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oxygen-depleted (on the way back to the lungs from tissues). Although it is a fluid, blood is thicker (more viscous) than water because it contains proteins and cells; it feels slightly oily and sticky for the same reason. Blood is slightly alkaline: pH averages about 7.40 (water is 7.0). Blood accounts for about 7% of body weightabout 5 kilograms (5 liters or 6 quarts of volume) in a 70-kg (155 lb) person. Before we explore the structure of blood in detail, lets take a look at its functions.

Blood elements form a clot to reduce blood loss.

Blood transfers heat to the skin surface to be lost. Blood elements defend against microbes entering body openings or wounds. Bloods hydraulic force sustains urine formation by kidneys.

Blood Has Five Main FunctionsIn the broadest sense, blood is a transportation system, truly an inner river that carries the essentials of life to tissues, returns metabolic wastes for elimination, and conveys chemical messages (Fig. 10.1). In particular, the functions of blood are: Transport. Blood transports gases (such as oxygen),

nutrients, waste products, and chemical messages between organs, tissues, and cells. Hydraulic force. This is the pressure created by fluid flowing in a closed space. Blood propelled out of the heart into blood vessels creates a form of hydraulic pressure called blood pressure. Without adequate blood pressure, human life is impossiblethe vital substances blood transports will not reach distant tissues. Moreover, blood pressure enables the kidney to make urine and provides the hydraulic force for male and female erection. Defense. Blood cells and other blood-borne substances defend against threats originating both externally (microbes) and internally (cancer). Heat transfer. The circulation of blood through the skin exposes blood to skin temperature, which is normally much cooler than the core temperature of organs, where the metabolism of nutrients generates heat. Warm blood passes through skin, heat is lost, and cooler blood returns to the body core. Prevention of blood loss. Blood cells and elements form short-lived blockages in damaged vessels in order to prevent blood loss following tissue injury.

Blood transports oxygen, nutrients, wastes, and chemical messengers.

Figure 10.1. Blood functions. The many functions of blood, as illustrated by a wounded hiker. The hikers face is flushed, reflecting increased blood flow. How does this increased superficial blood flow help him?

healing. Sometimes this worsened the patients illness or led to the loss of the patients life, as we discuss in the accompanying History of Science box, titled The History of Blood Transfusion.

Blood Is Composed of Plasma and Cellular ElementsAs we just noted, blood is composed of two main compartments: a fluid extracellular matrix called plasma and the solid cellular elements suspended within it. The cellular elements are whole blood cells and fragments of cells called platelets. Clinicians refer to plasma and its cellular components together as whole blood. Because the cellular elements are heavier (denser) than plasma, we can separate the two by centrifugation in a tubethe heavy cellular elements settle to the bottom of the tube

Until about 150 years ago, few physicians had more than a vague understanding of these functions and their relationship to health. Indeed, their fanciful theories of illness sometimes led them to bleed patients of large quantities of blood in a misguided effort to promote

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The History of Blood TransfusionThe circulation of blood in blood vessels through the body had been worked out correctly in the 13th century by an Arab physician named Ibn Al-Nafis. He rejected the prevailing view, originating in the second century with the Greek physician Galen, that bright red arterial blood originated in the heart and was consumed by the tissues, and that dark venous blood originated in the liver and served another purpose. Ibn Al-Nafiss findings were not known in Europe for centuries. Thus, the idea of blood flowing in blood vessels was not understood in the West until English physician William Harvey discovered the facts in 1628. Even before physicians understood the anatomy and physiology of the circulatory system, however, they made crude attempts to infuse blood into the sick. The first recorded attempt occurred in 1492, as Columbus was discovering the Americas. Pope Innocent VIII lay comatose in Rome and physicians attempted to rescue him by collecting blood from three 10-year-old boys and infusing it into the pope. Since the concept of blood circulating in veins had not yet been established, the blood was infused into his mouth. It was not a successthe Pope and all the boys died. In 1665, British physician Richard Lower devised instruments to shunt blood between surgically joined dogs. He observed that the ill effect of blood loss on one dog could be reversed by shunting the blood of a second dog into the first. A few years later, in 1668, Dr. Jean-Baptiste Denys, personal physician to King Louis XIV of France, transfused a small amount of sheeps blood into a 15year-old boy. The boy survived and the experiment was counted a success, but modern physicians recognize that his survival was likely due to the small amount of blood transfused. One of Dr. Denyss less fortunate patients survived two such transfusions but died after the third, amid great controversy. The first human-to-human intravascular blood transfusion would not occur for about another 150 years. In 1818, Dr. James Blundell, a British obstetrician caring for a woman who was hemorrhaging after

Blood transfusions. Direct person-to-person transfusions.

childbirth, recruited the patients husband as a donor and extracted four ounces (about 120 mL) of blood from the mans arm to transfuse into his wife. In the ensuing years, Dr. Blundell performed 10 additional transfusions, 5 of which were judged beneficial. For another 100 years, all attempts at blood transfusion were direct: from the body of one person directly into another. Two advancesblood banking and compatibility testingwere required before indirect blood transfusions could be widely used. In about 1918, perhaps stimulated by the awful carnage of World War I (19141918), it was discovered that blood could be anticoagulated, refrigerated, and stored (banked) for a few days before transfusion. But blood banking was of limited use until the concept of donor and recipient blood compatibility came to be understood. This leap forward can be attributed to the work of the Austrian scientist Karl Landsteiner. He discovered ABO blood groups in 1900, and, with his colleague Alexander Wiener, discovered the Rh blood group in 1937. With this discovery, all of the pieces were at last in place and modern transfusion practice spread widely.

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beneath the lighter liquid at the top (Fig. 10.2A). When we do this, heres what we see: At the top of our tube is plasma, the liquid part of

automated machines, and the procedure is typically referred to as a complete blood count (CBC).

Case Notes10.1. In Eleanors case, the initial blood analysis found that cellular elements accounted for about 27% of her blood volume. What percent of her blood volume was composed of plasma? 10.2. Based on the information in the previous case note, what was Eleanors approximate hematocrit?

blood, which accounts for about 55% of blood volume. It is a golden, syrupy mix composed mainly of water in which are dissolved proteins, nutrients, minerals, and other life essentials. At the bottom of the tube are red blood cells (clinically referred to as erythrocytes, erythro red), the heaviest and most numerous cells. They normally account for about 45% of blood volume, a percentage called the hematocrit (Greek haima blood; krites judge, as in someone who separates things, such as right from wrong). At the interface between plasma and red cells is a thin, tan layer, the buffy coat. This layer contains cells that are not as heavy as red cellswhite blood cells (clinically referred to as leukocytes, leuko white): these include monocytes, lymphocytes, neutrophils, eosinophils, and basophils. The buffy coat also contains platelets, fragments of a bone marrow cell called a megakaryocyte. The buffy coat normally accounts for less than 1% of blood volume.

Plasma Contains Water and SolutesPlasma is the extracellular fluid of blood. It is nearly identical to the interstitial fluid of solid tissues (Chapter 5) except for the large amount of blood proteins it contains. Transparent and straw-colored, plasma is about 90% water; about 9% is composed of specialized proteins. There are three major types of plasma proteins: Albumin. The most abundant (about 55%) of all plasma

Remember This! The two major compartments of blood are fluid (plasma) and solid matter (cellular elements).The cellular elements of blood are easily visualized by microscopic examination of a blood smear. In this procedure, the lab technician spreads a drop of blood thinly over a microscope slide (Fig. 10.2B) and then stains the smear with Wrights stain, a mixture of blue and red dyes that impart colors to the various elements of the cells. It includes hematoxylin, a dark blue, alkaline dye, which stains the nucleus blue, and eosin, a bright red, acidic dye, which stains the cytoplasm pale red or pink. Cell organelles may stain a mixture of red, blue, or neutral tan. Based on the size and shape of the cells, the presence or absence of a nucleus, and the color of cytoplasmic granules (if any), the various cellular elements can easily be identified (see Table 10.1 on page 383). In addition to centrifugation to determine the hematocrit, other laboratory procedures can be employed to count the number of red blood cells, white blood cells, and platelets; measure the average size of the red blood cells; determine the amount of oxygen-carrying hemoglobin in the red blood cells; and determine the percentage of the various subtypes of white blood cells. Typically these measurements are done as a group by

proteins is albumin. Albumin accounts for most of the plasma osmotic pressure (Chapter 3), the force that tends to hold water in blood and draw water across the blood vessel wall from tissues into the bloodstream. This ability to keep water inside blood vessels is very important in maintaining blood volume. Albumin also acts as a binding protein that transports fatty acids, steroids, and other substances in blood. Fibrinogen. Somewhat over 5% of plasma protein is fibrinogen, a small protein involved in blood clotting, as explained later in the text. Globulins. Most of the other blood proteins are globulins, a catchall category that includes specialized binding (transport) proteins, enzymes, protein hormones, and clotting factors. For example, transferrin is a special globulin that transports iron, an important function discussed further on. Of particular interest is a subgroup of globulins, the gamma globulins, also called antibodies, made by specialized white blood cells to attack harmful microbes. About 1% of plasma is a rich mixture of other solutes. These include:

Glucose Cholesterol and other lipids Vitamins and other essential compounds Calcium, iron, sodium, potassium, and other minerals Metabolic wastes Dissolved gases such as oxygen, nitrogen, and carbon dioxide.

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1Whole blood is withdrawn from a vein and transferred to a tube.

2Centrifugation separates blood elements by their density.

Buffy coat: